Collagen XXVII Organises the Pericellular Matrix in the Growth Plate

In order to characterise the function of the novel fibrillar type XXVII collagen, a series of mice expressing mutant forms of the collagen were investigated. Mice harboring a glycine to cysteine substitution in the collagenous domain were phenotypically normal when heterozygote and displayed a mild disruption of growth plate architecture in the homozygous state. Mice expressing an 87 amino acid deletion in the collagenous domain of collagen XXVII were phenotypically normal as heterozygotes whereas homozygotes exhibited a severe chondrodysplasia and died perinatally from a lung defect. Animals expressing the 87 amino acid deletion targeted specifically to cartilage were viable but severely dwarfed. The pericellular matrix of proliferative chondrocytes was disrupted and the proliferative cells exhibited a decreased tendency to flatten and form vertical columns. Collagen XXVII plays an important structural role in the pericellular extracellular matrix of the growth plate and is required for the organisation of the proliferative zone.为了表征新型纤维状XXVII型胶原（fibrillar type XXVII collagen）的功能，本研究对一系列表达该胶原突变体形式的小鼠开展了系统性分析。携带胶原结构域（collagenous domain）内甘氨酸向半胱氨酸替换突变的小鼠，杂合子表型正常，纯合子则表现出生长板结构的轻度紊乱。表达XXVII型胶原胶原结构域内87个氨基酸缺失突变的小鼠，杂合子表型无异常；而纯合子出现严重软骨发育异常，并因肺部缺陷于围产期死亡。特异性在软骨组织中表达该87氨基酸缺失突变的小鼠可存活，但呈现严重矮小表型。增殖软骨细胞的细胞周基质（pericellular matrix）遭到破坏，且增殖细胞扁平化并形成垂直柱状结构的倾向显著降低。XXVII型胶原在生长板的细胞周细胞外基质（extracellular matrix）中发挥关键结构功能，且是增殖区组织构建所必需的。